The object of the current proposed experiments is to explore the mechanism by which the major histocompatibility complex (MHC) influences T cell responses to antigen. Our approach will attempt a synthesis of several current lines of work in this area. Principally, it will focus on T cell idiotypy and on the restriction of mature T cell responses by the MHC. It will also involve an exploration of the relationship between the Ly antigen phenotype of effector T cells and the region (I or KD) of the murine MHC recognized by T cells of that type. From these experiments we hope to be able to make a detailed synthesis of the structure and genetic origin of the T cell receptor(s) for antigen. Functional studies will focus on the reactivity of purified alloreactive T cells for both modified self MHC antigens and for conventional antigens. Antigen driven suicide experiments should allow us to determine if T cells are precommitted in self MHC recognition, or whether priming is required to restrict T cell specificity for self MHC antigens. Responses to Mls locus antigens provide another method of studying MHC restriction in both primary and secondary T cell responses. To further define T cell antigen recognition, anti-idiotypic antisera against receptors for MHC antigens (KD or I) as well as against receptors for conventional antigens will be prepared. The anti-(anti-MHC) idiotypes will be used to positively select MHC reactive T cells which will then be tested for 1) funtional recognition of conventional antigens, and 2) presence of anti-(anti-conventional antigen) idiotypes.